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Mapping chicken flu virus offers clues about deadly H7N9 bird flu

After tracing the evolution of a flu virus that has plagued poultry farms in China for decades, an international team
suggests how the new avian flu virus H7N9 - that has sickened more than 375 people and killed 115 since 2013 - may have come
about.

Writing in the Proceedings of the National Academy of Sciences, the researchers - led by members from St. Jude
Children's Research Hospital in Memphis, TN, and China Agricultural University in Beijing - conclude it is important to keep an
eye on chicken flu viruses for signs of pandemic potential.

They found changes in the H9N2 chicken virus that could serve as an early warning signal of flu viruses with potential to
create a
human pandemic.

H9N2 is a chicken flu virus that causes the birds to lay fewer eggs and leaves them susceptible to other deadly
infections.

The researchers used whole genome sequencing to trace how the H9N2 chicken flu virus evolved from 1994 to 2013.

Key steps in the evolution of H9N2 likely gave H7N9 opportunity to emerge

From an analysis of thousands of sequences of H9N2's genetic code, they found its genetic diversity dropped sharply in 2009,
giving rise to a predominant subtype called G57. This subtype flourished despite widespread vaccination of birds against
H9N2.

The team believes this set the stage for the emergence of H7N9. Chickens infected with H9N2 became infected with other flu
viruses - perhaps carried by migratory birds. In these chickens, the various viruses swapped genes, allowing H7N9 to emerge with
six genes from H9N2.

Co-corresponding author Dr. Robert Webster, of the Department of Infectious Diseases at St. Jude, says their findings suggest
that "tracking genetic diversity of H9N2 on poultry farms could provide an early warning of emerging viruses with the potential
to spark a pandemic."

The study also examines the factors that could have led to the predominant H9N2 subtype.

Vaccination of poultry against H9N2 began in 1998, and for a decade it stopped flu outbreaks in chickens. The vaccine works by
targeting a protein called hemagglutinin (HA) that sits like a spike on the surface of the flu virus.

Changes in the flu virus genes can alter the shape of the HA spike - making it harder for the vaccine to recognize and bind
to it - thus diminishing its effectiveness and raising the risk of outbreaks.

Over time, natural mutations in HA that confer the virus this ability to evade the vaccine will lead to strains that
dominate.

Dominant H9N2 swapped genes with various flu viruses

In their study, the team tested the effectiveness of the H9N2 vaccine against the strains that dominated in 2010-11 and found
it neither protected chickens from infection nor prevented virus spread in vaccinated chickens.

The researchers believe the emergence of the dominant H9N2 strain was the first step in the creation of the H7N9 virus because it
raised the chances of H9N2 mixing with other flu strains and reassorting or swapping genes with them. They note that:

"It became predominant in vaccinated farm chickens and caused widespread outbreaks before the H7N9 virus emergence,
increasing reassortment between H9N2 and other subtype viruses and finally providing all of their internal genes to the novel
H7N9 viruses."

The genome sequencing also revealed that H9N2 had swapped genes with quail and duck flu viruses.

In July 2014, Medical News Today brought news of a study where researchers showed that tackling immune response could be a promising new direction for flu drugs. In the Journal
of Virology, they describe how they found such an approach might be effective in fighting infection by the H7N9 avian flu
virus.

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